Restriction fragment length polymorphism (RFLP) analysis of the human genome is a powerful method to identify host genetic factors that influence host resistance or susceptibility to infection and disease. We are using this method, in combination with the methodologies of population genetics and epidemiology, to examine genetic influence on the outcomes of infections by HIV and hepatitis B virus (HBV). HIV infection is clearly associated with a number of neoplasms including Kaposi's sarcoma (KS) and lymphomas. HBV is the primary etiologic agent for hepatocellular carcinoma, a major neoplasm and cause of death in subSaharan Africa and China where HBV infection is common. We are attempting to identify genes that influence viral infection and disease progression by using RFLP markers of both anonymous and candidate loci distributed throughout the genome. Distortions in population genetic equilibrium between dichotomous outcomes may identify genetic factors that provide predisposition to different outcomes to infection by viral pathogens. Distortions in population genetic equilibrium between dichotomous case-controls will identify putative genetic factors that provide a predisposition to certain disease outcomes to viral infection. We have identified and acquired 550 clones that detect human polymorphisms at a resolution of 2-10 centiMorgans. We have received 2,228 specimens from different HIV risk groups and 1,200 case-control specimens from a Chinese HBV cohort. Preliminary results suggest that there are significant differences in allele frequencies between Blacks and Caucasians for 35% of the probes analyzed to date. In an analysis of a small number of HIV seropositive Caucasians with and without AIDS, an association with four RFLP markers was found.